tbuckley/cabot-search huggingface dataset:
Analysis of Obstetric Outcomes by Hospital Location, Volume, and Teaching Status Associated With Non–Medically Indicated Induction of Labor at 39 Weeks
Authors: Alyssa R. Hersh, Kimberley A. Bullard, Bharti Garg, Megha Arora, Brooke F. Mischkot, Aaron B. Caughey
Journal: JAMA Network Open (2023)

Non-medically indicated induction of labor has been demonstrated to potentially improve some obstetric outcomes, such as decreasing cesarean birth. It has been reported that rates of cesarean birth and other obstetric outcomes vary among hospitals with different characteristics.To assess whether obstetric outcomes differ between nulliparous individuals with low-risk pregnancies managed with non-medically indicated induction of labor compared with expectant management in different types of hospitals.This retrospective cohort study included non-medically indicated induction of labor at 39 weeks' gestation compared with expectant management of singleton, nonanomalous, births in nulliparous women with low-risk pregnancies in California between January 1, 2007, and December 31, 2011. The initial analysis of these data was performed in 2021. Outcomes were assessed by 3 hospital characteristics: location (urban vs rural), obstetric volume, and teaching (academic vs community) status. Volume was categorized based on the average number of births per year and grouped into low (<1200 births per year), medium (1200-2399 births per year), and high (≥2400 births per year). Births with previous or planned cesarean delivery were excluded, and non-medically indicated induction of labor was defined as induction of labor without a specific medical indication. Testing with χ2 and multivariable logistic regression analyses was used for statistical comparisons with a cutoff level of P = .01.Non-medically indicated induction of labor at 39 weeks' gestation.The primary outcome was cesarean birth, and numerous secondary perinatal outcomes were also assessed.There were 455 044 births included in this study. When stratified by hospital variables, a number of sociodemographic characteristics were significantly different, such as race and ethnicity, age, body mass index, and insurance type. The adjusted odds ratios (aORs) of cesarean birth were significantly lower in all settings with induction of labor except for low-volume hospitals, in which there was no significant difference (aOR, 0.95; 95% CI, 0.82-1.09). Chorioamnionitis and postpartum hemorrhage were lower with induction of labor among nearly every hospital when stratified by hospital characteristics. Neonatal outcomes were improved in all settings with induction of labor compared with expectant management.These findings suggest that non-medically indicated induction of labor may be associated with a lower rate of cesarean births and some maternal and neonatal adverse outcomes in a range of hospital settings.
Nanoparticle‐Based MRI‐Guided Tumor Microenvironment Heating via the Synergistic Effect of Ferroptosis and Inhibition of TGF‐<i>β</i> Signaling
Authors: Rui Zhou, Yantan Liu, Zhaojun Wang, Jinyu Lv, Wangjun Liao, Zheyu Shen, Xiaoxiang Rong
Journal: Advanced Healthcare Materials (2023)

Although induction of ferroptosis and inhibition of transforming growth factor-β (TGF-β) signaling are both effective ways to reform the tumor microenvironment (TME) and render low-immunogenic tumors responsive to immune checkpoint inhibitor therapy, dose-limiting side effects remain major obstacles hindering their clinical application. Herein, novel sorafenib and anti-TGF-β antibody loaded Fe3 O4 /Gd2 O3 hybrid nanoparticles with conjugation of arginine-glycine-aspartic dimer (FeGd-HN@Sorafenib@TGF-β-antibody@RGD2, FG-STR) are developed. Sorafenib significantly enhances FeGd-HN-triggered ferroptosis and improves maturation and phagocytosis of dendritic cells (DCs) by inducing damage-associated molecular patterns released from ferroptotic cancer cells, while the anti-TGF-β antibody further synergizes with enhanced ferroptosis to promote DC maturation and the recruitment of CD8+ T cells, thus heating the TME. Moreover, the incorporation of RGD2 facilitates the uptake of the FG-STR in tumor cells which lead to a significant dosage reduction of both sorafenib and anti-TGF-β antibody to avoid dose-limiting toxicities. Finally, in vitro and in vivo experiments show that FG-STR has significantly superior intrinsic magnetic resonance imaging (MRI) capability than that of Gadovist, effectively inhibits tumor growth and lung metastasis, and increases the efficacy of anti-programmed cell death-1 treatment. Taken together, this study provides a promising strategy for new advanced MRI-guided TME heating therapies.
Abrocitinib as a novel treatment for lichen sclerosus
Authors: Chengbei Bao, Qiuyun Xu, Zhixun Xiao, Haiqing Wang, Renwei Luo, Bo Cheng, Chao Ji, Ting Gong
Journal: British Journal of Dermatology (2023)

Ten patients were recruited to evaluate the efficacy and safety of abrocitinib for the treatment of lichen sclerosus (LS). All patients reported rapid control of pruritus at week 2 and achieved Investigator’s Global Assessment 0 or 1 at week 12. This study suggests that the abrocitinib could be an effective and safe treatment option for LS, based on the significant improvements seen in investigator evaluations, patient-reported outcomes and skin imaging findings.
Combined inhibition of BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance of TP53-mutant acute myeloid leukemia to individual BH3 mimetics
Authors: Bing Z. Carter, Po Yee Mak, Wenjing Tao, Edward Ayoub, Lauren B. Ostermann, Xuelin Huang, Sanam Loghavi, Steffen Boettcher, Yuki Nishida, Vivian Ruvolo, Paul E. Hughes, Phuong K. Morrow, Torsten Haferlach, Steven Kornblau, Muharrem Muftuoglu, Michael Andreeff
Journal: Blood Cancer Journal (2023)

Abstract TP53 -mutant acute myeloid leukemia (AML) respond poorly to currently available treatments, including venetoclax-based drug combinations and pose a major therapeutic challenge. Analyses of RNA sequencing and reverse phase protein array datasets revealed significantly lower BAX RNA and protein levels in TP53 -mutant compared to TP53– wild-type (WT) AML, a finding confirmed in isogenic CRISPR-generated TP53 -knockout and -mutant AML. The response to either BCL-2 (venetoclax) or MCL-1 (AMG176) inhibition was BAX-dependent and much reduced in TP53 -mutant compared to TP53 -WT cells, while the combination of two BH3 mimetics effectively activated BAX, circumventing survival mechanisms in cells treated with either BH3 mimetic, and synergistically induced cell death in TP53 -mutant AML and stem/progenitor cells. The BH3 mimetic–driven stress response and cell death patterns after dual inhibition were largely independent of TP53 status and affected by apoptosis induction. Co-targeting, but not individual targeting of BCL-2 and MCL-1 in mice xenografted with TP53 -WT and TP53 -R248W Molm13 cells suppressed both TP53 -WT and TP53 -mutant cell growth and significantly prolonged survival. Our results demonstrate that co-targeting BCL-2 and MCL-1 overcomes BAX deficiency-mediated resistance to individual BH3 mimetics in TP53 -mutant cells, thus shifting cell fate from survival to death in TP53 -deficient and -mutant AML. This concept warrants clinical evaluation.
Reciprocal Changes and Emergent Trips to the Catheterization Laboratory
Authors: Mochamad Yusuf Alsagaff, Terrence Timothy Evan Lusida, Muhammad Ramadhan
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Medicare Skilled Nursing Facility Use and Spending Before and After Introduction of the Public Health Emergency Waiver During the COVID-19 Pandemic
Authors: Agne Ulyte, R. J. Waken, Arnold M. Epstein, E. John Orav, Michael L. Barnett, Karen E. Joynt Maddox, David C. Grabowski
Journal: JAMA Internal Medicine (2023)

In response to the COVID-19 pandemic, Medicare introduced a public health emergency (PHE) waiver in March 2020, removing a 3-day hospitalization requirement before fee-for-service beneficiaries could receive skilled nursing facility (SNF) care benefits.
Safety, usability, and performance of a wireless left atrial pressure monitoring system in patients with heart failure: the <scp>VECTOR‐HF</scp> trial
Authors: Domenico D'Amario, David Meerkin, Attilio Restivo, Hüseyin Ince, Horst Sievert, Andrea Wiese, Ulrich Schaefer, Carlo Trani, Antoni Bayes‐Genis, Francisco Leyva, Zachary I. Whinnett, Carlo Di Mario, Michael Jonas, Habib Manhal, Ignacio J. Amat‐Santos, Maria Del Trigo, Tuvia Ben Gal, Binyamin Ben Avraham, Tal Hasin, Sebastian Feickert, Giuseppe D'Ancona, Omar Abdul‐Jawad Altisent, Oran Koren, Oren Caspi, William T. Abraham, Filippo Crea, Stefan D. Anker, Ran Kornowski, Leor Perl
Journal: European Journal of Heart Failure (2023)

In heart failure (HF), implantable haemodynamic monitoring devices have been shown to optimize therapy, anticipating clinical decompensation and preventing hospitalization. Direct left-sided haemodynamic sensors offer theoretical benefits beyond pulmonary artery pressure monitoring systems. We evaluated the safety, usability, and performance of a novel left atrial pressure (LAP) monitoring system in HF patients.The VECTOR-HF study (NCT03775161) was a first-in-human, prospective, multicentre, single-arm, clinical trial enrolling 30 patients with HF. The device consisted of an interatrial positioned leadless sensor, able to transmit LAP data wirelessly. After 3 months, a right heart catheterization was performed to correlate mean pulmonary capillary wedge pressure (PCWP) with simultaneous mean LAP obtained from the device. Remote LAP measurements were then used to guide patient management. The miniaturized device was successfully implanted in all 30 patients, without acute major adverse cardiac and neurological events (MACNE). At 3 months, freedom from short-term MACNE was 97%. Agreement between sensor-calculated LAP and PCWP was consistent, with a mean difference of -0.22 ± 4.92 mmHg, the correlation coefficient and the Lin's concordance correlation coefficient values were equal to 0.79 (p < 0.0001) and 0.776 (95% confidence interval 0.582-0.886), respectively. Preliminary experience with V-LAP-based HF management was associated with significant improvements in New York Heart Association (NYHA) functional class (32% of patients reached NYHA class II at 6 months, p < 0.005; 60% of patients at 12 months, p < 0.005) and 6-min walk test distance (from 244.59 ± 119.59 m at baseline to 311.78 ± 129.88 m after 6 months, p < 0.05, and 343.95 ± 146.15 m after 12 months, p < 0.05).The V-LAP™ monitoring system proved to be generally safe and provided a good correlation with invasive PCWP. Initial evidence also suggests possible improvement in HF clinical symptoms.
A Phase I/II Trial of HER2 Vaccine–Primed Autologous T-Cell Infusions in Patients with Treatment Refractory HER2–Overexpressing Breast Cancer
Authors: Mary L. Disis, Yushe Dang, Andrew L. Coveler, Jennifer S. Childs, Doreen M. Higgins, Ying Liu, Jing Zhou, Sean Mackay, Lupe G. Salazar
Journal: Clinical Cancer Research (2023)

Abstract Purpose: High levels of type I T cells are needed for tumor eradication. We evaluated whether the HER2-specific vaccine–primed T cells are readily expanded ex vivo to achieve levels needed for therapeutic infusion. Patients and Methods: Phase I/II nonrandomized trial of escalating doses of ex vivo–expanded HER2-specific T cells after in vivo priming with a multiple peptide–based HER2 intracellular domain (ICD) vaccine. Vaccines were given weekly for a total of three immunizations. Two weeks after the third vaccine, patients underwent leukapheresis for T-cell expansion, then received three escalating cell doses over 7- to 10-day intervals. Booster vaccines were administered after the T-cell infusions. The primary objective was safety. The secondary objectives included extent and persistence of HER2-specific T cells, development of epitope spreading, and clinical response. Patients received a CT scan prior to enrollment and 1 month after the last T-cell infusion. Results: Nineteen patients received T-cell infusions. Treatment was well tolerated. One month after the last T-cell infusion, 82% of patients had significantly augmented T cells to at least one of the immunizing epitopes and 81% of patients demonstrated enhanced intramolecular epitope spreading compared with baseline (P &amp;lt; 0.05). There were no complete responses, one partial response (6%), and eight patients with stable disease (47%), for a disease control rate of 53%. The median survival for those with progressive disease was 20.5 months and for responders (PR+SD) was 45.0 months. Conclusions: Adoptive transfer of HER2 vaccine–primed T cells was feasible, was associated with minimal toxicity, and resulted in an increased overall survival in responding patients. See related commentary by Crosby et al., p. 3256
First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Xiaojiang Duan, Lei Xia, Zhuochen Zhang, Yanan Ren, Martin G. Pomper, Steven P. Rowe, Xuesong Li, Nan Li, Ning Zhang, Hua Zhu, Zhi Yang, Xinan Sheng, Xing Yang
Journal: Clinical Cancer Research (2023)

Nectin-4 is an emerging biomarker for cancer diagnosis and therapy. Recently, enfortumab vedotin (EV) was approved by the FDA as the first nectin-4 targeting antibody-drug conjugate for treating advanced urothelial carcinoma (UC). A PET imaging method to noninvasively quantify nectin-4 expression level would potentially help to select patients most likely to respond to EV and predict the response.In this study, we designed a bicyclic peptide-based nectin-4 targeting radiotracer 68Ga-N188. Initially, we performed preclinical evaluations of 68Ga-N188 in UC cell lines and xenograft mouse models. Next, we performed the translational study in healthy volunteers and a pilot cohort of patients with advanced UC on uEXPLORER total-body PET/CT.In the preclinical study, 68Ga-N188 showed high affinity to nectin-4, specific uptake in a nectin-4(+) xenograft mouse model, and suitable pharmacokinetic and safety profiles. In the translational study, 2 healthy volunteers and 14 patients with advanced UC were enrolled. The pharmacokinetic profile was determined for 68Ga-N188, and the nectin-4 relative expression level in different organs was quantitatively imaged.A clear correlation between PET SUV value and nectin-4 expression was observed, supporting the application of 68Ga-N188 PET as a companion diagnostic tool for optimizing treatments that target nectin-4. See related commentary by Jiang et al., p. 3259.
Reimagining the journey to recovery: The COVID-19 pandemic and global mental health
Authors: Vikram Patel, Daisy Fancourt, Toshi A. Furukawa, Lola Kola
Journal: PLoS Medicine (2023)

In this editorial, guest editors Vikram Patel, Daisy Fancourt, Lola Kola, and Toshi Furukawa discuss the contents of the special issue on the pandemic and global mental health, highlighting key themes and providing important context.
Reciprocal Changes and Emergent Trips to the Catheterization Laboratory
Authors: Santi Di Pietro, Bruno Barcella, Stefano Perlini
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia
Authors: Christina Glytsou, Xufeng Chen, Emmanouil Zacharioudakis, Wafa Al-Santli, Hua Zhou, Bettina Nadorp, Soobeom Lee, Audrey Lasry, Zhengxi Sun, Dimitrios Papaioannou, Michael Cammer, Kun Wang, Tomasz Zal, Malgorzata Anna Zal, Bing Z. Carter, Jo Ishizawa, Raoul Tibes, Aristotelis Tsirigos, Michael Andreeff, Evripidis Gavathiotis, Iannis Aifantis
Journal: Cancer Discovery (2023)

Abstract BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetic therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3 mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 overexpression is sufficient to drive resistance to BH3 mimetics in AML. Insensitivity to BH3 mimetics is accompanied by enhanced mitochondria–endoplasmic reticulum interactions and augmented mitophagy flux, which acts as a prosurvival mechanism to eliminate mitochondrial damage. Genetic or pharmacologic MFN2 targeting synergizes with BH3 mimetics by impairing mitochondrial clearance and enhancing apoptosis in AML. Significance: AML remains one of the most difficult-to-treat blood cancers. BH3 mimetics represent a promising therapeutic approach to eliminate AML blasts by activating the apoptotic pathway. Enhanced mitochondrial clearance drives resistance to BH3 mimetics and predicts poor prognosis. Reverting excessive mitophagy can halt BH3-mimetic resistance in AML. This article is highlighted in the In This Issue feature, p. 1501
Validation of eGFR for Detecting Associations Between Serum Protein Biomarkers and Subsequent GFR Decline
Authors: Inger T. T. Enoksen, Nikoline B. Rinde, Dmitri Svistounov, Jon V. Norvik, Marit D. Solbu, Bjørn O. Eriksen, Toralf Melsom
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement eGFR from creatinine, cystatin C, or both has been primarily used in search of biomarkers for GFR decline. Whether the relationships between biomarkers and eGFR decline are similar to associations with measured GFR (mGFR) decline has not been investigated. This study revealed that some biomarkers showed statistically significant different associations with eGFR decline compared with mGFR decline, particularly for eGFR from cystatin C. The findings indicate that non–GFR-related factors, such as age, sex, and body mass index, influence the relationship between biomarkers and eGFR decline. Therefore, the results of biomarker studies using eGFR, particularly eGFRcys, should be interpreted with caution and perhaps validated with mGFR. Background Several serum protein biomarkers have been proposed as risk factors for GFR decline using eGFR from creatinine or cystatin C. We investigated whether eGFR can be used as a surrogate end point for measured GFR (mGFR) when searching for biomarkers associated with GFR decline. Methods In the Renal Iohexol Clearance Survey, GFR was measured with plasma iohexol clearance in 1627 individuals without diabetes, kidney, or cardiovascular disease at baseline. After 11 years of follow-up, 1409 participants had one or more follow-up GFR measurements. Using logistic regression and interval-censored Cox regression, we analyzed the association between baseline levels of 12 serum protein biomarkers with the risk of accelerated GFR decline and incident CKD for both mGFR and eGFR. Results Several biomarkers exhibited different associations with eGFR decline compared with their association with mGFR decline. More biomarkers showed different associations with eGFRcys decline than with eGFRcre decline. Most of the different associations of eGFR decline versus mGFR decline remained statistically significant after adjustment for age, sex, and body mass index, but several were attenuated and not significant after adjusting for the corresponding baseline mGFR or eGFR. Conclusions In studies of some serum protein biomarkers, eGFR decline may not be an appropriate surrogate outcome for mGFR decline. Although the differences from mGFR decline are attenuated by adjustment for confounding factors in most cases, some persist. Therefore, proposed biomarkers from studies using eGFR should preferably be validated with mGFR.
Context and Differentiation in Antidepressant Effects of Physical Activity in Children and Adolescents—Reply
Authors: Francesco Recchia, Joshua D. K. Bernal, Parco M. Siu
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal